GPR curation for C5-branched dibasic acid metabolism and Glucocorticoid biosynthesis

[JHL-452b]

Current behavior:

9 genes are discovered to be uncorrelated with their corresponding reactions in C5-branched dibasic acid metabolism and Glucocorticoid biosynthesis.

Gene	UniProtID	Reaction	GPR	Correlation	Manually check
ENSG00000172340	Q96I99	MAR08662: CoA + GTP + itaconate <=> GDP + itaconyl-CoA + Pi	(ENSG00000163541 and ENSG00000172340) or (ENSG00000136143 and ENSG00000163541)	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000172340 encodes an enzyme that functions specifically in the citric acid cycle (TCA), catalyzing the conversion involving succinyl-CoA, GTP, and succinate. In contrast, the provided reaction involves itaconate and the formation of itaconyl-CoA, which is not part of the TCA cycle or the reaction catalyzed by the product of this gene. Thus, the enzymatic activities and substrates do not match, indicating irrelevance.	No Yes
ENSG00000172340	Q96I99	MAR08663: ADP + itaconyl-CoA + Pi <=> ATP + CoA + itaconate	(ENSG00000163541 and ENSG00000172340) or (ENSG00000136143 and ENSG00000163541)	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000172340 encodes for a GTP-specific succinyl-CoA synthetase that participates in the citric acid cycle (TCA) by coupling the hydrolysis of succinyl-CoA to the synthesis of GTP. This specific enzyme activity is characterized by the reaction: CoA + GTP + succinate = GDP + phosphate + succinyl-CoA. On the other hand, the reaction provided is ADP + itaconyl-CoA + Pi <=> ATP + CoA + itaconate, which involves converting itaconyl-CoA to itaconate and does not pertain to the catalysis of succinyl-CoA or the specific substrate-level phosphorylation described for the gene product. Therefore, the gene and the reaction are not related based on their specific functions and substrates involved.	No Yes
ENSG00000172340	Q96I99	MAR08667: ADP + mesaconyl-CoA + Pi <=> ATP + CoA + mesaconate	(ENSG00000163541 and ENSG00000172340) or (ENSG00000136143 and ENSG00000163541)	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000172340 codes for an enzyme that functions in the TCA cycle, catalyzing the reaction where CoA, GTP, and succinate are converted to GDP, phosphate, and succinyl-CoA. In contrast, the provided reaction involves ADP, mesaconyl-CoA, and Pi being converted to ATP, CoA, and mesaconate, which does not involve the substrates or products specific to the enzyme encoded by the gene. This discrepancy suggests that the gene and the given reaction are not related.	No
ENSG00000197580	Q9BYV7	MAR01985: 17alpha-hydroxyprogesterone + NADPH + O2 --> 4-androstene-3,17-dione + acetate + H2O + NADP+	ENSG00000148795 or ENSG00000197580	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197580 encodes a mitochondrial dioxygenase that primarily mediates the oxidative cleavage of carotenoids into various products. The annotated functions and catalytic activities listed for this gene involve reactions with carotenoids such as all-trans-beta-carotene, lycopene, zeaxanthin, and beta-cryptoxanthin, among others. These reactions include the specific oxidative cleavage of these carotenoids at certain carbon-carbon double bonds. However, the reaction provided involves the conversion of 17alpha-hydroxyprogesterone into 4-androstene-3,17-dione, acetate, H2O, and NADP+, a process unrelated to carotenoid metabolism. Thus, this gene's role in carotenoid cleavage does not overlap with the biochemical transformation of 17alpha-hydroxyprogesterone, making it irrelevant to the reaction provided.	No
ENSG00000197580	Q9BYV7	MAR01987: 17alpha-hydroxyprogesterone + NADPH + O2 <=> 4-androstene-3,17-dione + acetate + H2O + NADP+	ENSG00000148795 or ENSG00000197580	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197580 functions as a mitochondrial dioxygenase that specifically cleaves carotenoids such as all-trans-beta-carotene, lycopene, zeaxanthin, lutein, and beta-cryptoxanthin, and is involved in carotenoid metabolism. The reaction provided involves the conversion of 17alpha-hydroxyprogesterone to 4-androstene-3,17-dione, acetate, H2O, and NADP+, which is unrelated to the cleavage of carotenoids. Therefore, the gene does not participate in the reaction described.	No
ENSG00000197580	Q9BYV7	MAR02000: cortisol + H+ + 2.0 NADPH + O2 --> 11beta-hydroxyandrost-4-ene-3,17-dione + acetate + 2.0 H2O + 2.0 NADP+	ENSG00000148795 or ENSG00000160882 or ENSG00000179142 or ENSG00000197580	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197580 encodes a mitochondrial dioxygenase involved in the oxidative cleavage of carotenoids, mediating reactions that transform carotenes and xanthophylls into various apocarotenals and ionones. In contrast, the provided reaction involves the conversion of cortisol to 11beta-hydroxyandrost-4-ene-3,17-dione, a process requiring NADPH and producing acetate, H2O, and NADP+. This cortisol-related reaction does not involve carotenoids or the specific catalytic activities of the dioxygenase encoded by ENSG00000197580, indicating no relevance between the gene and the reaction.	No
ENSG00000197580	Q9BYV7	MAR02001: cortisol + H+ + 2.0 NADPH + O2 --> 11beta-hydroxyandrost-4-ene-3,17-dione + acetate + 2.0 H2O + 2.0 NADP+	ENSG00000148795 or ENSG00000160882 or ENSG00000179142 or ENSG00000197580	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197580 is associated with the mitochondrial dioxygenase enzyme that cleaves carotenoids such as all-trans-beta-carotene, lycopene, zeaxanthin, lutein, and beta-cryptoxanthin. Its reactions involve the oxidative cleavage of these carotenoids. In contrast, the reaction described involves the conversion of cortisol using NADPH and O2, resulting in different products not related to carotenoid metabolism. Therefore, the gene and the provided reaction are not related.	No
ENSG00000213614	P06865	MAR07587: 3.0 H2O + n2m2nmn --> (alpha-D-mannosyl)2-beta-D-mannosyl-N-acetylglucosamine + 3.0 N-acetylglucosamine	ENSG00000049860 or ENSG00000169660 or ENSG00000213614	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000213614 codes for an enzyme that hydrolyzes terminal non-reducing N-acetyl-D-hexosamine residues in various substrates, such as glycoconjugates, glycolipids, and gangliosides. The provided reaction involves the hydrolysis of n2m2nmn into (alpha-D-mannosyl)2-beta-D-mannosyl-N-acetylglucosamine and N-acetylglucosamine, which does not align with the specific catalytic activities described for the gene's enzyme. Therefore, the gene's enzyme cannot catalyze the provided reaction.	No
ENSG00000125779	Q9BZ23	MAR04731: (R)-4-phosphopantothenoyl-cysteine + ADP + H+ <=> ATP + N-pantothenoylcysteine	ENSG00000120137 or ENSG00000125779 or ENSG00000152782	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000125779 encodes for an enzyme that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of CoA synthesis. However, the reaction provided (R)-4-phosphopantothenoyl-cysteine + ADP + H+ <=> ATP + N-pantothenoylcysteine involves different substrates and products and does not describe the phosphorylation of pantothenate or the synthesis of 4'-phosphopantothenate. Therefore, the gene and the reaction are not related based on the provided annotation.	No

[hhl-24]

keep gene ENSG00000172340 for reaction MAR08662 and MAR08663. In mitochondria, itaconate can be converted by succinate-coenzyme A (CoA) ligase to itaconyl-CoA at the expense of ATP (or GTP).See 1

for reaction MAR08667, ENSG00000163541, ENSG00000136143 and ENSG00000163541 should also be removed.

I am not sure whether to remove ENSG00000213614 for MAR07587, as well as ENSG00000049860 and ENSG00000169660.

[hhl-24]

for reaction MAR04731, ENSG00000120137 and ENSG00000152782 should also be removed.

[JHL-452b]

for reaction MAR08667, ENSG00000163541, ENSG00000136143 and ENSG00000163541 should also be removed.
for reaction MAR04731, ENSG00000120137 and ENSG00000152782 should also be removed.

Why do you think these genes are not connected to the reactions? Can you give a reason?

[hhl-24]

for reaction MAR08667, ENSG00000163541, ENSG00000136143 and ENSG00000163541 should also be removed.
for reaction MAR04731, ENSG00000120137 and ENSG00000152782 should also be removed.

Why do you think these genes are not connected to the reactions? Can you give a reason?

Because the genes in the GPR of these reactions have the same function, but there are clear specifications for the substrates, the reactants included in these reactions are not within the scope.